BOL-148

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Chemical compound

title: "BOL-148" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["5-ht2b-antagonists", "antimigraine-drugs", "bromoarenes", "carboxamides", "diethylamino-compounds", "experimental-non-hallucinogens", "hallucinogen-antidotes", "lysergamides", "methyl-compounds", "non-hallucinogenic-5-ht2a-receptor-agonists", "psychedelic-lysergamides", "psychoplastogens", "serotonin-receptor-antagonists"] description: "Chemical compound" topic_path: "general/5-ht2b-antagonists" source: "https://en.wikipedia.org/wiki/BOL-148" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

| Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 477212727 | drug_name = BOL-148 | image = 2-bromo-LSD_structure.svg | image_class = skin-invert-image | width = 175px | image2 = BOL-148 3D.png | image_class2 = bg-transparent | width2 = 200px

| tradename = | routes_of_administration = Oral | class = Serotonin receptor agonist; Non-hallucinogenic serotonin 5-HT2A receptor agonist

| legal_AU = | legal_CA = | legal_UK = | legal_status = Not scheduled (United States, Canada, Germany, EU precursors)

| bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =

| CAS_number_Ref = | CAS_number = 478-84-2 | UNII_Ref = | UNII = JUA77QEU32 | ChemSpiderID_Ref = | ChemSpiderID = 9765 | ChEMBL_Ref = | ChEMBL = 274384 | IUPHAR_ligand = 272 | PubChem = 10171 | PDB_ligand = A1AFU | synonyms = BOL148; BOL; 2-Bromo-LSD; 2-Br-LSD; 2-bromolysergic acid diethylamide; Bromolysergide; Bromine-LSD; BETR-001; BTR001; TD-0148A; TD0148A; NYPRG-101; NYPRG101; 2-Bromo-N,N-diethyllysergamide; 2-Bromo-N,N-diethyl-6-methyl-9,10-didehydroergoline-8β-carboxamide

| IUPAC_name = (6aR,9R)-5-bromo-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide | C = 20 | H = 24 | Br = 1 | N = 3 | O = 1 | SMILES = CCN(CC)C(=O)[C@H]1CN([C@@H]2CC3=C(NC4=CC=CC(=C34)C2=C1)Br)C | StdInChI_Ref = | StdInChI = 1S/C20H24BrN3O/c1-4-24(5-2)20(25)12-9-14-13-7-6-8-16-18(13)15(19(21)22-16)10-17(14)23(3)11-12/h6-9,12,17,22H,4-5,10-11H2,1-3H3/t12-,17-/m1/s1 | StdInChIKey_Ref = | StdInChIKey = VKRAXSZEDRWLAG-SJKOYZFVSA-N

BOL-148, also known as 2-bromo-LSD or as bromolysergide, is a non-hallucinogenic serotonin receptor modulator of the lysergamide family related to the psychedelic drug lysergic acid diethylamide (LSD). It is specifically the 2-bromo derivative of LSD.

The drug is a non- or minimally-hallucinogenic serotonin 5-HT2A receptor partial agonist, as well as acting at other targets such as other serotonin receptors and dopamine receptors. The lack of psychedelic effects with BOL-148 is thought to be due to lower-efficacy partial agonism at the serotonin 5-HT2A receptor compared to LSD that is insufficient to produce hallucinogenic effects. The drug has been found to produce psychoplastogenic and antidepressant-like effects in animals.

BOL-148 was initially developed by Albert Hofmann in the 1950s, as part of the original research from which LSD was also derived. It is now being reinvestigated and is under development for the potential treatment of cluster headaches and other conditions. This is under new developmental code names including BETR-001, TD-0148A, and NYPRG-101.

Use and effects

Clinical studies have found that unlike LSD, BOL-148 lacks hallucinogenic effects in humans at doses considered to be moderate to high. In addition, some but not all clinical studies of BOL-148 in combination with LSD have found BOL-148 to block the psychedelic effects of LSD.

However, some isolated incidents of hallucinogenic responses with BOL-148 have been reported. There is one case report of LSD-like delirium with BOL-148, and very high doses of BOL-148 have been reported to produce mild mental changes as well as LSD-like subjective effects. It may be that BOL-148, rather than being fully non-hallucinogenic, is actually mild psychedelic at sufficiently high doses. In any case, as with other non-hallucinogenic LSD analogues such as lisuride, hallucinogenic effects with BOL-148 appears to be a rare side effect occurring only in individuals with an as yet unexplained susceptibility to this reaction.

Interactions

Pharmacology

Pharmacodynamics

BOL-148 was found to be inactive as a psychedelic and so was comparatively little researched for many years, although its similar behaviour in the body made it useful for radiolabelling studies. It was found to bind to many of the same receptors as LSD, but acting as a neutral antagonist rather than an agonist. BOL-148 reportedly attenuates the effects of LSD in humans.

In 2023, BOL-148 was characterised as a non-hallucinogenic serotonin 5-HT2A receptor biased partial agonist and as a serotonin 5-HT2B receptor antagonist. It shows weaker partial agonism of the serotonin 5-HT2A receptor than LSD (Emax = 60% vs. 92%, respectively). Unlike LSD, BOL-148 fails to produce the head-twitch response, a behavioural proxy of psychedelic effects, in animals. In addition, BOL-148 blocked the head-twitch response of the psychedelic DOI.

BOL-148 shows weak recruitment of β-arrestin2 and has reduced potential to induce tolerance in the form of serotonin 5-HT2A receptor downregulation. Similarly to LSD, the drug was also found to interact with numerous other serotonin receptors and targets. However, BOL-148 reportedly shows less off-target activity compared to LSD. In animals, BOL-148 shows psychoplastogenic (i.e., neuroplasticity-enhancing) effects and antidepressant-like effects.

The cryo-EM structures of the serotonin 5-HT2A receptor with BOL-148, as well as with various serotonergic psychedelics and other serotonin 5-HT2A receptor agonists, have been solved and published by Bryan L. Roth and colleagues.

Chemistry

Analogues

Analogues of BOL-148 (2-bromo-LSD) include 2-iodo-LSD (IOL, MBL-61 (MOB-61; 1-methyl-2-bromo-LSD), 1-methyl-2-iodo-LSD (MIL), 2-oxo-LSD, and bromocriptine, among others. 1P-BOL-148 (1-propionyl-2-bromo-LSD; SYN-L-017) is an ester prodrug of BOL-148.

Development

The generally similar behaviour of BOL-148 to LSD in some respects has shown to be very useful in potential the treatment of cluster headaches. These debilitating attacks have been known for some time to be amenable to treatment with certain hallucinogenic drugs such as LSD and psilocybin, but because of the illegal status of these drugs and the kind of mental changes they induce, research into their medical use has been slow and therapeutic application limited to very specific circumstances under strict supervision. It had been thought that this specific therapeutic action against cluster headaches was limited to hallucinogenic drugs of this type, and would always present a major barrier to their clinical use. However, a serendipitous discovery found that BOL-148 can also produce this therapeutic effect, despite lacking the other effects of LSD. This has led to a resurgence of interest and research into BOL-148 and its possible medical uses.

BOL-148, under the developmental code name BETR-001 (previously TD-0148A), is under development by BetterLife Pharma for the treatment of cluster headaches and other indications. A prodrug of BOL-148, under the developmental code name SPT-348, is also under development by Seaport Therapeutics for the treatment of depression, anxiety, and other neuropsychiatric disorders.

References

References

  1. "BOL-148 hydrochloride". THC Pharm GmbH.
  2. (19 January 2021). "BetterLife Confirms Non-Controlled Status of 2-bromo-LSD with Health Canada - Psilocybin Alpha". Psychedelic Alpha.
  3. (November 2023). "Beyond the 5-HT2A Receptor: Classic and Nonclassic Targets in Psychedelic Drug Action". J Neurosci.
  4. (October 2024). "Chemistry/structural biology of psychedelic drugs and their receptor(s)". Br J Pharmacol.
  5. (September 2022). "Psychedelics as preventive treatment in headache and chronic pain disorders". Neuropharmacology.
  6. (March 2023). "A non-hallucinogenic LSD analog with therapeutic potential for mood disorders". Cell Rep.
  7. (1957). "Substitutionen am Ringsystem der Lysergsäure. III. Halogenierung. 45. Mitteilung über Mutterkornalkaloide". Helvetica Chimica Acta.
  8. (May 2025). "Are the LSD-analogs lisuride and ergotamine examples of non-hallucinogenic serotonin 5-HT2A receptor agonists?". Journal of Psychopharmacology.
  9. Fanchamps, A.. (1978). "Ergot Alkaloids and Related Compounds". Springer Berlin Heidelberg.
  10. (July 1956). "Prevention of psychological effects of d-lysergic acid diethylamide (LSD 25) by its 2-brom derivative (BOL 148)". Nature.
  11. (November 1959). "Cross tolerance between D-2-brom-lysergic acid diethylamide (BOL-148) and the D-diethylamide of lysergic acid (LSD-25)". Psychopharmacologia.
  12. (2019). "The Serotonin System".
  13. (April 2011). "Is BOL-148 hallucinogenic?". Cephalalgia.
  14. (1967). "A possible correlation between drug-induced hallucinations in man and a behavioural response in mice". Psychopharmacologia.
  15. (December 2022). "ACNP 61st Annual Meeting: Poster Abstracts P271-P540: P358. A Non-Hallucinogenic LSD Analog With Therapeutic Potential for Mood Disorders". Neuropsychopharmacology.
  16. (March 2025). "The structural diversity of psychedelic drug actions revealed". Nature Communications.
  17. (September 2022). "Structures of Hallucinogenic and Non-Hallucinogenic Analogues of the 5-HT2A Receptor Reveals Molecular Insights into Signaling Bias".
  18. (September 2010). "The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: an open, non-randomized case series". Cephalalgia.
  19. (29 August 2024). "BETR 001".
  20. (14 October 2024). "Delving into the Latest Updates on Bromolysergide with Synapse".
  21. (8 May 2025). "Delving into the Latest Updates on SPT-348 with Synapse".
  22. (June 2024). "Next-generation psychedelics: should new agents skip the trip?". Nat Biotechnol.
  23. Psychedelic Alpha. (1 May 2025). "March & April 2025 Psychedelic Patent Update: Lykos' Patent Woes Continue; Filings Provide First Look at Seaport's 2-Bromo-LSD Program; Delix's Ergoline Analogues; CaaMTech's Spinout".
  24. (11 May 2025). "New lipid prodrugs of bromolysergide disclosed in Seaport Therapeutics patent".

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5-ht2b-antagonistsantimigraine-drugsbromoarenescarboxamidesdiethylamino-compoundsexperimental-non-hallucinogenshallucinogen-antidoteslysergamidesmethyl-compoundsnon-hallucinogenic-5-ht2a-receptor-agonistspsychedelic-lysergamidespsychoplastogensserotonin-receptor-antagonists